Technical Abstract:
Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar, Neuroimmunomod 2009;16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expression of cytokines and the glucocorticoid receptor (GR) in isolated peripheral blood mononuclear cells (PBMCs). Brahman heifers (n=12; 334±12 kg BW) had jugular catheters inserted prior to a challenge with 0.1 IU/kg BW ACTH. Blood samples were collected into EDTA vacutainers at -3, 0, 1, 2, and 4 hr relative to the challenge. Plasma cortisol was determined by RIA. PBMCs were isolated via density gradient centrifugation and frozen at -80oC until RNA isolation. Extracted RNA was amplified by real-time RT-PCR to determine expression of GR, tumor necrosis factor-alpha (TNF), interferon-gamma (IFN), interleukin-4 (IL-4), and IL-10. Cytokine expression data are expressed as the fold change in gene expression relative to samples collected at cannulation or time 0. All data were analyzed using the Mixed procedure of SAS, with time and animal as class and random variables, respectively. There was a tendency for cortisol concentrations to decrease between cannulation (-3 hr) and initiation of the ACTH challenge (time 0 hr; 26.2±4.4 and 16.1±4.4 ng/mL, respectively; P=0.07). Expression of most genes only tended to increase (P=0.06-0.14), with the exception of IFN (P=0.05), which increased 16-fold relative to expression at cannulation. In response to ACTH, cortisol concentrations peaked at 1 hr (52.4±2.77 ng/mL; P<0.01) before decreasing to pre-challenge values. Expression of IL-10 followed a similar pattern, with the greatest fold increase in expression at 1 hr (3.9±0.7 fold; P=0.02). Expression of GR, IL-4, and TNF increased through 4 hr post-challenge (9-92 fold; P=0.01-0.04). Expression of IFN tended to increase in response to ACTH challenge (28-fold; P=0.06). This suggests that stimuli that increase endogenous cortisol concentrations may influence the expression of cytokines, and therefore modulate the immune system.